Arenaviruses and filoviruses are among the most lethal and destructive viruses. They cause severe, often fatal viral hemorraghic fevers in humans and nonhuman primates (e.g., monkeys, gorillas, and chimpanzees). Both genera of viruses are of particular concern as possible biological weapons since they have the potential for aerosol dissemination and weaponization.
The incubation period for Filovirus infection ranges from 2 to 21 days. The onset of illness is abrupt and is characterized by high fever, headaches, joint and muscle aches, sore throat, fatigue, diarrhea, vomiting, and stomach pain. A rash, red eyes, hiccups and internal and external bleeding may be seen in some patients. Within one week of becoming infected with the virus, most patients experience chest pains and multiple organ failure, go into shock, and die. Some patients also experience blindness and extensive bleeding before dying.
Filoviridae are a family of RNA viruses. Two members of the Filoviridae family have been identified: Ebola virus (EBOV) and Marburg virus (MARV). There is one identified strain of MARV and four identified subtypes (i.e., strains) of EBOV: Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast (i.e., Ebola-Tai), and Ebola-Reston. The exact origin, locations, and natural habitat of Filoviridae are unknown. However, on the basis of available evidence and the nature of similar viruses, it is postulated that Filoviridae are zoonotic (i.e., animal-borne) and are normally maintained in an animal host that is native to the African continent.
For more than 30 years, EBOV has been associated with periodic episodes of hemorrhagic fever in Central Africa that produce severe disease in infected patients. Mortality rates in outbreaks have ranged from 50% for the Sudan species of EBOV (SEBOV) to up to 90% for the Zaire species of EBOV (ZEBOV) (Sanchez et al., Filoviridae: Marburg and Ebola Viruses, in Fields Virology (eds. Knipe, D. M. & Howley, P. M.) 1409-1448 (Lippincott Williams & Wilkins, Philadelphia)). An outbreak late in 2007 caused by an apparently new species of EBOV in Uganda resulted in a fatality rate of about 25% (Towner et al., PLoS Pathog., 4:e1000212 (2008)). ZEBOV has also decimated populations of wild apes in this same region of Africa (Walsh et al., Nature, 422:611-614 (2003)).
Arenaviridae are also a family of RNA viruses. Arenaviruses can be divided into two serogroups, which differ genetically and by geographical distribution: the lymphocytic choriomeningitis virus (LCMV)-Lassa virus (Old World) complex and the Tacaribe virus (New World) complex. Lassa virus (LASV) causes lassa fever, which is an acute viral hemorrhagic fever first described in 1969 in the town of Lassa, in Borno State, Nigeria. The infection is endemic in West African countries, and causes 300,000-500,000 cases annually, with approximately 5,000 deaths. Outbreaks of the disease have been observed in Nigeria, Liberia, Sierra Leone, Guinea, and the Central African Republic, but it is believed that human infections also exist in Democratic Republic of the Congo, Mali, and Senegal.
Prevention and treatment of viral infections responsible for causing hemorraghic fevers presents many challenges. In fact, there are no vaccines or postexposure treatment modalities available for preventing or managing such infections. Patients instead receive supportive therapy, i.e., electrolyte and fluid balancing, oxygen, blood pressure maintenance, and treatment for any secondary infections.
Thus, there is a need for compositions and methods for treating and preventing viral infections, e.g., by specifically modulating viral or host genes involved in hemorraghic fever. The present invention addresses these and other needs.